Cancer is gradually becoming the leading disease-related cause of death of the human population. Thus, there is an ultimate need for innovation in drug discovery and development, especially in the area of oncology. Unfortunately, clinical attrition rates are a critical issue in drug development, particularly in oncology where over fourfold higher rates of attrition were determined in respect to other indications .
Although, this trend presumably relates to the substantial heterogeneity and the inherent biological complexity of cancer, in order to track the source of this failure it should be interesting to chart the drug targets that researchers have traditionally focused on. It could be then realized that one of the fundamental issues that drove to this decline in pharmaceutical research and development is the philosophy that shaped the drug discovery process. The one-gene-one-disease theory sculpted the drug design concept to treat diseases by targeting individual chemoreceptors with a magic-bullet therapy. Drugs were thus traditionally rationally designed and tailored to target rigid protein binding pockets on the basis of complementarity, the so-called lock-and-key mechanism. This unidimensional approach on proteins presenting compact and well-ordered 3D architectures lead presently to the majority of druggable targets: G-protein-coupled receptors (GPCRs) and enzymes.
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Andreas G. Tzakos: Intrinsic Protein Disorder as a Drug Target in Oncology: Designing Drugs Targeting Plasticity.
Last date updated on November, 2020